Links of Sleep Duration with Biomarkers of Accelerated Aging: the Baltimore Longitudinal Study of Aging

Sleep disorders and sleep deprivation have been linked to markers of biological aging, including methylation change and increases in white blood cell and neutrophil counts. However, little is known regarding the association of sleep duration with biological markers of aging. We investigated links of self-reported sleep duration with biological aging markers in 615 participants in the Baltimore Longitudinal Study of Aging (BLSA) aged ≥50 years (mean = 71.0 ± 11.2, 49.6% women, 68.8% white) with data on self-reported sleep duration in hours (i.e., ≤6 (n=131), >6 to 7 (n=234), >7 (n=250)), demographics, and genetic and methylation data (mDNA). Our aging biomarker outcomes were four epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge), mDNA-estimated PAI1, and estimated granulocyte count. After adjustment for age, sex, and race, compared to those sleeping ≤6 hours, those reporting >7 hours of sleep had faster biological aging according to Hannum age-acceleration, PhenoAge, GrimAge, mDNA-estimated PAI1, and granulocyte count. In addition, sleep duration interacted with age, such that compared to individuals reporting ≤6 hours of sleep, individuals reporting >6 to 7 hours showed lower GrimAge with increasing age, and with sex, such that males with longer sleep duration (>6 to 7 and >7 hours) showed a lower granulocyte count compared to females. Findings suggest that both short and long sleep duration are associated with and may contribute to accelerated aging. Prospective studies in larger samples are needed to examine whether changes in sleep duration precede changes in aging biomarkers.

Salazosulfapyridine-induced agranulocytosis in a patient on chronic hemodialysis with seronegative spondyloarthropathy: a case report

Background Salazosulfapyridine is a generally safe drug often used to treat rheumatoid arthritis and ulcerative colitis. However, agranulocytosis is a rare but serious adverse effect of this drug. To date, there have been no reports describing the clinical course of salazosulfapyridine-induced agranulocytosis in a chronic hemodialysis patient. Case presentation The patient was a 64-year-old man with IgA nephropathy who had been on chronic hemodialysis for about 3 years. For 1 month, he had general fatigue, mild fever, and pain in multiple joints of the upper extremities. He was hospitalized and underwent detailed examinations in our department. Laboratory investigations revealed an erythrocyte sedimentation rate of 67 mm/h and a C-reactive protein level of 7.73 mg/dL. Rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Musculoskeletal ultrasonography showed inflammation of the tendon sheath in both wrists and the right shoulder joint. Computed tomography scans revealed osteosclerosis and narrowing of the sacroiliac joint. The diagnosis was seronegative spondyloarthropathy. He was started on salazosulfapyridine. Four weeks later, he had a high fever and low granulocyte count. Treatment with granulocyte colony-stimulating factor was started. The agranulocytosis could not be ascribed to any other cause and was considered an adverse effect of salazosulfapyridine, which was then stopped. Nine days later, the granulocyte count had recovered and the fever had resolved. Conclusions Currently, there are no guidelines on the use of salazosulfapyridine in chronic hemodialysis patients. The starting dosage should be smaller for these patients than for patients without renal impairment. Also, the laboratory monitoring interval for complete blood count should be shorter than usual.

Role of Manual Immature to Total Neutrophil (I/T) Ratio and Automated Immature Granulocyte Count (IGC) and Percentage (IG%) in the Early Diagnosis of Neonatal Sepsis

Background: The diagnosis of neonatal sepsis is challenging due to non-specific and subtle clinical features, low sensitivity and delay in routine laboratory tests. Current study was conducted to evaluate the role of manual immature/total (I/T) neutrophil ratio and automated immature granulocyte count (IGC) and immature granulocyte percentage (IG%) in the diagnosis of neonatal sepsis. Materials and Methods: An analytical cross-sectional study was done during a period of 6 months with a sample of 55 neonates admitted to Colombo South Teaching Hospital, Sri Lanka. A combination of clinical and laboratory parameters including full blood count, C-reactive protein and blood culture were used to identify the neonates with probable sepsis. The population was subcategorized into five (5) groups and manual immature/total neutrophil (I/T) ratio, immature granulocyte count (IGC) and immature granulocyte%(IG%) were done in each neonate. Results: The sensitivity of manual I/T ratio was 93.75% and negative predictive value (NPV) was 95.24%. The sensitivity for lower cut off values, IGC of 0.03x103/µL and IG% of 0.5% was 80% and 73.33% respectively. The NPV for above cut-off values were 25% and 0.5% respectively. The NPV was improved with higher cut-off values with 70.90% for IGC 0.3 and 70.59% for IG 3%, but sensitivity remained low with 40% and 33.33% respectively.Conclusion: Manual I/T ratio remains as a useful diagnostic tool in diagnosing and excluding neonatal sepsis with a very good sensitivity and NPV. However, further studies and well defined reference intervals are required in automated IGC and IG%.

White blood cells and severe COVID-19: a Mendelian randomization study

BackgroundThe pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged to seriously threaten public health. We aimed to investigate whether white blood cell traits have potential causal effects on severe COVID-19 using Mendelian randomization (MR).MethodsTo evaluate the causal associations between various white blood cell traits and severe COVID-19, we conducted a two-sample MR analysis with summary statistics from recent large genome-wide association studies.ResultsOur MR results indicated potential causal associations of white blood cell count, myeloid white blood cell count, and granulocyte count with severe COVID-19, with odds ratios (OR) of 0.84 (95% CI: 0.72-0.98), 0.81 (95% CI: 0.70-0.94), and 0.84 (95% CI: 0.71-0.99), respectively. Increasing eosinophil percentage of white blood cells was associated with a higher risk of severe COVID-19 (OR: 1.22, 95% CI: 1.03-1.45).ConclusionsOur results suggest the potential causal effects of lower white blood cell count, lower myeloid white blood cell count, lower granulocyte count, and higher eosinophil percentage of white blood cells on an increased risk of severe COVID-19.